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CD103+CD56+ ILCs Are Associated with an Altered CD8+ T-cell Profile within the Tumor Microenvironment

6 hours 58 minutes ago
Immunotherapies have had unprecedented success in the treatment of multiple cancer types, albeit with variable response rates. Unraveling the complex network of immune cells within the tumor microenvironment (TME) may provide additional insights to enhance antitumor immunity and improve clinical response. Many studies have shown that NK cells or innate lymphoid cells (ILC) have regulatory capacity. Here, we identified CD103 as a marker that was found on CD56+ cells that were associated with a...
Douglas C Chung

Metabolic signaling of ceramides through the FPR2 receptor inhibits adipocyte thermogenesis

1 day 6 hours ago
Ceramides play a central role in human health and disease, yet their role as systemic signaling molecules remain poorly understood. In this work, we identify FPR2 as a membrane receptor that specifically binds long-chain ceramides (C14-C20). In brown and beige adipocytes, C16:0 ceramide binding to FPR2 inhibits thermogenesis via G(i)-cyclic AMP signaling pathways, an effect that is reversed in the absence of FPR2. We present three cryo-electron microscopy structures of FPR2 in complex with G(i)...
Hui Lin

Canadian consensus for the assessment and testing of Lynch syndrome

1 day 6 hours ago
CONCLUSION: This is the first comprehensive Canadian guideline for LS providing guidance to genetic specialists, laboratories, primary care providers and healthcare providers caring for patients with LS. It is endorsed by the Canadian College of Medical Genetics and the Canadian Association of Genetic Counsellors. The consensus statements are presented as a model for standard of care that improves equitable access to health services for LS across the country. Future work should include a...
Melyssa Aronson

Mediation CNN (Med-CNN) Model for High-Dimensional Mediation Data

1 day 6 hours ago
Complex biological features such as the human microbiome and gene expressions play a crucial role in human health by mediating various biomedical processes that influence disease progression, such as immune responses and metabolic processes. Understanding these mediation roles is essential for gaining insights into disease pathogenesis and improving treatment outcomes. However, analyzing such high-dimensional mediation features presents challenges due to their inherent structural and...
Yao Li

Landscapes of missense variant impact for human superoxide dismutase 1

4 days 6 hours ago
Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease for which important subtypes are caused by variation in the Superoxide Dismutase 1 gene SOD1. Diagnosis based on SOD1 sequencing can not only be definitive but also indicate specific therapies available for SOD1-associated ALS (SOD1-ALS). Unfortunately, SOD1-ALS diagnosis is limited by the fact that a substantial fraction (currently 26%) of ClinVar SOD1 missense variants are classified as "variants of uncertain...
Anna Axakova

The role of amylin, a gut-brain axis hormone, in metabolic and neurological disorders

4 days 6 hours ago
Amylin, also known as islet amyloid polypeptide (IAPP), is a pancreatic β-cell peptide hormone involved in satiation and control food intake. It is also produced in smaller quantities by neurons, the gastrointestinal tract, and spinal ganglia. Numerous studies have revealed that patients with type 2 diabetes mellitus (T2DM) and cognitive deficits exhibit IAPP deposits in the pancreas, brain, and blood vessels. IAPP has also been shown to exert neuroprotective effects against Alzheimer's disease...
Tahir Muhammad

Neuron-specific repression of alternative splicing by the conserved CELF protein UNC-75 in C. elegans

4 days 6 hours ago
Tissue-regulated alternative exons are dictated by the interplay between cis-elements and trans-regulatory factors such as RNA binding proteins. Despite extensive research on splicing regulation, the full repertoire of these cis and trans features and their evolutionary dynamics across species are yet to be fully characterized. Members of the CUG-binding protein and ETR-like family (CELF) of RNA binding proteins are known to play a key role in the regulation of tissue-biased splicing patterns,...
Pallavi Pilaka-Akella

Language models for protein design

1 week ago
The recent surge of large language models has shown that machines are capable of reading, understanding, and communicating through language, even sometimes displaying capabilities surpassing those of humans. Proteins can be represented as strings of amino acids akin to words in a sentence, and the same principles of language modeling can be used to learn informative representations for protein structure prediction, design, and property prediction. In this review, we will focus on applications of...
Jin Sub Lee

Internet-Based Cognitive Behavioral Therapy for Preventing Postpartum Depressive Symptoms Among Pregnant Individuals With Depression: Multicenter Randomized Controlled Trial in China

1 week ago
CONCLUSIONS: Among individuals with antenatal depression, ICBT did not prevent the development of PPD. However, ICBT may be a preferable option for those with mild to moderate antenatal depressive symptoms. Future research is needed to explore modifications to ICBT to address more severe depressive symptoms.
Chen-Chi Duan

Cross-kingdom-mediated detection of intestinal protozoa through NLRP6

1 week 2 days ago
Intestinal protists are detected by the host innate immune system through mechanisms that remain poorly understood. Here, we demonstrate that Tritrichomonas protozoa induce thickening of the colonic mucus in an NLRP6-, ASC-, and caspase-11-dependent manner, consistent with the activation of sentinel goblet cells. Mucus growth is recapitulated with cecal extracts from Tritrichomonas-infected mice but not purified protozoa, suggesting that NLRP6 may detect infection-induced microbial dysbiosis. In...
Nathaniel J Winsor

iModEst: disentangling -omic impacts on gene expression variation across genes and tissues

1 week 2 days ago
Many regulatory factors impact the expression of individual genes including, but not limited, to microRNA, long non-coding RNA (lncRNA), transcription factors (TFs), cis-methylation, copy number variation (CNV), and single-nucleotide polymorphisms (SNPs). While each mechanism can influence gene expression substantially, the relative importance of each mechanism at the level of individual genes and tissues is poorly understood. Here, we present the integrative Models of Estimated gene expression...
Dustin J Sokolowski

From FAIR to CURE: Guidelines for Computational Models of Biological Systems

1 week 3 days ago
Guidelines for managing scientific data have been established under the FAIR principles requiring that data be Findable, Accessible, Interoperable, and Reusable. In many scientific disciplines, especially computational biology, both data and models are key to progress. For this reason, and recognizing that such models are a very special type of "data", we argue that computational models, especially mechanistic models prevalent in medicine, physiology and systems biology, deserve a complementary...
Herbert M Sauro

Synergistic RAS-MAPK and AKT Activation in MYC-Driven Tumors via Adjacent PVT1 Rearrangements

1 week 4 days ago
MYC-driven (MYC+) cancers are aggressive and often fatal. MYC dysregulation is a key event in these cancers, but overexpression of MYC alone is not always enough to cause cancer. Plasmocytoma Variant Translocation 1 (PVT1), a long non-coding RNA (lncRNA) adjacent to MYC on chromosome 8 is a rearrangement hotspot in many MYC+ cancers. In addition to being co-amplified with MYC, the genomic rearrangement at PVT1 involves translocation, which has had obscure functional consequences. We report that...
Ashutosh Tiwari

Sex differences in biomarkers and biologic mechanisms in psoriatic diseases and spondyloarthritis

1 week 4 days ago
Psoriasis and spondyloarthritis (SpA), including psoriatic arthritis (PsA), are immune-mediated inflammatory conditions that affect the skin and musculoskeletal system. Males and female patients with psoriatic disease and SpA exhibit differences in clinical presentation, disease progression, and treatment response. The underlying biological mechanisms driving these sex differences remain poorly understood. This review explores the current evidence on sex-related differences in biomarkers and...
Steven Dang

Dietary fibre counters the oncogenic potential of colibactin-producing Escherichia coli in colorectal cancer

1 week 4 days ago
Diet, microbiome, inflammation and host genetics have been linked to colorectal cancer development; however, it is not clear whether and how these factors interact to promote carcinogenesis. Here we used Il10^(-/-) mice colonized with bacteria previously associated with colorectal cancer: enterotoxigenic Bacteroides fragilis, Helicobacter hepaticus or colibactin-producing (polyketide synthase-positive (pks^(+))) Escherichia coli and fed either a low-carbohydrate (LC) diet deficient in soluble...
Bhupesh Kumar Thakur

Arabidopsis research in 2030: Translating the computable plant

1 week 4 days ago
Plants are essential for human survival. Over the past three decades, work with the reference plant Arabidopsis thaliana has significantly advanced plant biology research. One key event was the sequencing of its genome 25 years ago, which fostered many subsequent research technologies and datasets. Arabidopsis has been instrumental in elucidating plant-specific aspects of biology, developing research tools, and translating findings to crop improvement. It not only serves as a model for...
Siobhan Brady

Electrostatics of salt-dependent reentrant phase behaviors highlights diverse roles of ATP in biomolecular condensates

1 week 4 days ago
Liquid-liquid phase separation (LLPS) involving intrinsically disordered protein regions (IDRs) is a major physical mechanism for biological membraneless compartmentalization. The multifaceted electrostatic effects in these biomolecular condensates are exemplified here by experimental and theoretical investigations of the different salt- and ATP-dependent LLPSs of an IDR of messenger RNA-regulating protein Caprin1 and its phosphorylated variant pY-Caprin1, exhibiting, for example, reentrant...
Yi-Hsuan Lin

Spatial Variations of Atmospheric Alkylated Polycyclic Aromatic Hydrocarbons across the Western Pacific to the Southern Ocean: Unexpected Increasing Deposition

1 week 4 days ago
Spatial variations of atmospheric alkylated polycyclic aromatic hydrocarbons (Alk-PAHs) are key to understanding their long-range atmospheric transport (LRAT). However, limited Alk-PAHs data have hindered their LRAT characterizations on a global scale. In this study, 49 Alk-PAHs were measured in the atmospheric samples collected across the Western Pacific to the Southern Ocean. The summed concentration of 39 frequently detected Alk-PAHs (Σ(39)Alk-PAHs) was 25.8 ± 25.3 ng m^(-3). The...
Fu-Jie Zhu

Dimension Reduction Using Local Principal Components for Regression-Based Multi-SNP Analysis in 1000 Genomes and the Canadian Longitudinal Study on Aging (CLSA)

1 week 6 days ago
For genetic association analysis based on multiple SNP regression of genotypes obtained by dense DNA sequencing or array data imputation, multi-collinearity can be a severe issue causing failure to fit the regression model. In this study, we propose a method of Dimension Reduction using Local Principal Components (DRLPC) which aims to resolve multi-collinearity by removing SNPs under the assumption that the remaining SNPs can capture the effect of a removed SNP due to high linear dependency....
Fatemeh Yavartanoo

Search for Magnetic Monopole Pair Production in Ultraperipheral Pb+Pb Collisions at sqrt[s_{NN}]=5.36  TeV with the ATLAS Detector at the LHC

2 weeks ago
This Letter presents a search for highly ionizing magnetic monopoles in 262 μb^{-1} of ultraperipheral Pb+Pb collision data at sqrt[s_{NN}]=5.36 TeV collected by the ATLAS detector at the LHC. A new methodology that exploits the properties of clusters of hits reconstructed in the innermost silicon detector layers is introduced to study highly ionizing particles in heavy-ion data. No significant excess above the background, which is estimated using a data-driven technique, is observed. Using a...
G Aad